Vitexin protects isoproterenol induced post myocardial injury by modulating hipposignaling and ER stress responses

• Published in: Biochemical and biophysical research communications 2018-02, Vol.496 (2), p.731-737
• Main Authors: Ashokkumar, Rathinavel, Jamuna, Sankar, Sakeena Sadullah, M.S., Niranjali Devaraj, S.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - therapeutic use; Apigenin - therapeutic use; Apoptosis; Apoptosis - drug effects; Cardiotonic Agents - therapeutic use; Caspase 3 - metabolism; Endoplasmic Reticulum Stress - drug effects; ER stress; Hippo signaling; Isoproterenol; Male; Myocardial Infarction - chemically induced; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; Post MI; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats, Wistar; Signal Transduction - drug effects; UPR; Vitexin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.01.104

The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3. Moreover, post treatment with Vitexin inhibits the ISO induced translocation of CHOP to nucleus during MI. Further results have demonstrated that, activation of Mst1 through ER stress was diminished upon treatment with Vitexin. In addition to this, Vitexin treatment significantly downregulated the expression of p-Yap and p-Mst1 which were enhanced during post myocardial injury. Taken together, our data indicate that co-ordinated activation of ER stress and hipposignaling by ISO was ameliorated by the potent cardioprotective effects of Vitexin. •Vitexin exerts anti oxidant effect in Isoproterenol induced myocardial injury.•ISO induced apoptosis was ameliorated by post treatment with Vitexin.•Vitexin downregulates master regulator of hippo signaling Mst1 in post myocardial injury.•Co-ordinated activation of ER stress and hippo signaling was alleviated by Vitexin treatment.